Hypertension is one of the risk factors for strokes, heart attacks, heart failure and arterial aneurysm, and is a leading cause of chronic renal failure. Even moderate elevation of arterial blood pressure leads to shortened life expectancy.
Hypertension may be treated by targeting Angiotensin I-converting enzyme (ACE). ACE is an enzyme that participates in the body's renin-angiotensin system (RAS). It is an exopeptidase which catalyzes the conversion of the decapeptide angiotensin Ito the octapeptide angiotensin II. Angiotensin II causes blood vessels to constrict, and drives blood pressure up. It also stimulates the release of aldosterone from the adrenal cortex. Aldosterone promotes sodium retention in the distal nephron, in the kidney, which also drives blood pressure up.
ACE inhibitors are inter alia used for controlling blood pressure, treating heart failure, preventing strokes, and preventing kidney damage in people with hypertension or diabetes. They also improve survival after heart attacks. Commonly used ACE inhibitors include benazepril (Lotensin®), captopril (Capoten®), enalapril (Vasotec®), fosinopril (Monopril®), lisinopril (Prinivil®, Zestril®), moexipril (Univasc®), perindopril (Aceon®), quinapril (Accupril®), ramipril (Altace®), and trandolapril (Mavik®). These drugs often have undesired side effects and/or they are not effective enough, so there remains a need for further ACE inhibitors.
A number of different peptides have been found to have ACE-inhibitory activity (Vercruysse et al. September 2005, Journal of Agricultural and Food Chemistry A-J) and there remains a need to further peptides having ACE-inhibitory activity.